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<title>19 March, 2024</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<ul>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Lateral Flow Assays Biotesting by Utilizing Plasmonic Nanoparticles Made of Inexpensive Metals - Replacing Colloidal Gold</strong> -
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<div>
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Nanoparticles (NPs) can be conjugated with diverse biomolecules and employed in biosensing to detect target analytes in biological samples. This proven concept was primarily used during the COVID-19 pandemic with gold NPs-based lateral flow assays (LFAs). Considering the gold price and its worldwide depletion, here we show that novel plasmonic nanoparticles (NPs) based on inexpensive metals, titanium nitride (TiN) and copper covered with a gold shell (Cu@Au), perform comparable or even better than gold nanoparticles. After conjugation, these novel nanoparticles provided high figures of merit for LFA testing, such as high signals and specificity and robust naked-eye signal recognition. To the best of our knowledge, our study represents the 1st application of laser-ablation-fabricated nanoparticles (TiN) in the LFA and dot-blot biotesting. Since the main cost of the Au NPs in commercial testing kits is in the colloidal synthesis, our development with TiN is very exciting, offering potentially very inexpensive plasmonic nanomaterials for various bio-testing applications. Moreover, our machine learning study showed that the bio-detection with TiN is more accurate than that with Au.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.01.08.574723v2" target="_blank">Lateral Flow Assays Biotesting by Utilizing Plasmonic Nanoparticles Made of Inexpensive Metals - Replacing Colloidal Gold</a>
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</div></li>
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<li><strong>Identification of unique and potent inhibitors of SARS-CoV-2 main protease from DNA-encoded chemical libraries</strong> -
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<div>
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In vitro screening of large libraries of compounds with automated High-throughput screening is expensive, time consuming and requires dedicated infrastructures. Conversely, the screening of DNA-encoded chemical libraries can be rapidly performed with basic equipment available in most laboratories. In this study we identified novel inhibitors of SARS-CoV-2 main protease (Mpro) through the affinity screening of the commercially available ''DELopen'' library, containing 4.2 billion compounds. The identified inhibitors were peptidomimetics compounds containing a C-terminal electrophilic group able to covalently bind to Mpro reactive Cys145 (confirmed by x-ray crystallography). Compound SLL11 had IC50 = 30nM and was found to be well optimized, proving that the rapid exploration of large chemical spaces, enabled by DECL technology, allows the direct identification of potent inhibitors avoiding several rounds of iterative medicinal chemistry. Compound MP6, a close analogue of SLL11, showed antiviral activity against SARS-CoV-2 in the low micromolar range when tested in Caco-2 and Calu-3 (EC50 = 2.3 M) cell lines. As peptidomimetics compounds can suffer from low cell permeability and metabolic stability, the cyclization of the compounds as well as the substitution of selected residues with D-enantiomers will be explored in the future to improve the antiviral activity of these novel compounds.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.03.16.585341v1" target="_blank">Identification of unique and potent inhibitors of SARS-CoV-2 main protease from DNA-encoded chemical libraries</a>
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</div></li>
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<li><strong>A Protein Language Model for Exploring Viral Fitness Landscapes</strong> -
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<div>
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Successively emerging SARS-CoV-2 variants lead to repeated epidemic surges through escalated spreading potential (i.e., fitness). Modeling genotype-fitness relationship enables us to pinpoint the mutations boosting viral fitness and flag high-risk variants immediately after their detection. Here, we introduce CoVFit, a protein language model able to predict the fitness of variants based solely on their spike protein sequences. CoVFit was trained with genotype-fitness data derived from viral genome surveillance and functional mutation data related to immune evasion. When limited to only data available before the emergence of XBB, CoVFit successfully predicted the higher fitness of the XBB lineage. Fully-trained CoVFit identified 549 fitness elevation events throughout SARS-CoV-2 evolution until late 2023. Furthermore, a CoVFit-based simulation was able to predict the higher fitness of JN.1 subvariants before their detection. Our study provides both insight into the SARS-CoV-2 fitness landscape and a novel tool potentially transforming viral genome surveillance.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.03.15.584819v1" target="_blank">A Protein Language Model for Exploring Viral Fitness Landscapes</a>
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<li><strong>Modulation of SARS-CoV-2 spike binding to ACE2 throughconformational selection</strong> -
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The first step of SARS-CoV-2 infection involves the interaction between the trimeric viral spike protein () and the host angiotensin-converting enzyme 2 (2). The receptor binding domain () of adopts two conformations: open and closed, respectively, accessible and inaccessible to 2. Therefore, motions are suspected to affect 2 binding; yet a quantitative description of the underlying mechanism has been elusive. Here, using single-molecule approaches, we visualize opening and closing and probe the /2 interaction. Our results show that RBD dynamics affect 2 binding but not unbinding. The resulting modulation is quantitatively predicted by a conformational selection model in which each protomer behaves independently. Our work reveals a general molecular mechanism affecting binding affinity without altering binding strength, helping to understand coronavirus infection and immune evasion.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.03.15.585207v1" target="_blank">Modulation of SARS-CoV-2 spike binding to ACE2 throughconformational selection</a>
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</div></li>
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<li><strong>Binding of SARS-CoV-2 nucleocapsid protein to uninfected epithelial cells induces antibody-mediated complement deposition</strong> -
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<div>
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SARS-CoV-2 infection triggers strong antibody response toward Nucleocapsid-Protein (NP), suggesting extracellular presence beyond its intra-virion RNA binding. Interestingly, NP was found to decorate infected and proximal uninfected cell-surfaces. Here, we propose a new mechanism through which extracellular NP on uninfected cells contributes to COVID-19 pathogenicity. We show that NP binds to cell-surface sulfated linear-glycosaminoglycans by spatial rearrangement of its RNA-binding sites facilitated by the flexible, positively charged, linker. Coating of uninfected lung-derived cells with purified NP attracted anti-NP-IgG from lung fluids and sera collected from COVID-19 patients. The magnitude of this immune recognition was significantly elevated in moderate compared to mild COVID-19 cases. Importantly, binding of anti-NP-IgG present in sera generated clusters that triggered C3b deposition by the classical complement pathway. Heparin analog enoxaparin outcompeted NP-binding, rescuing cells from anti-NP IgG-mediated complement deposition. Our findings unveil how extracellular NP may exacerbate COVID-19 tissue damage, and suggest leads for preventative therapy.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.03.17.585388v1" target="_blank">Binding of SARS-CoV-2 nucleocapsid protein to uninfected epithelial cells induces antibody-mediated complement deposition</a>
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</div></li>
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<li><strong>CORACLE (COVID-19 liteRAture CompiLEr): A platform for efficient tracking and extraction of SARS-CoV-2 and COVID-19 literature, with examples from post-COVID with respiratory involvement</strong> -
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<div>
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Background: During COVID-19 pandemic there emerged a need to efficiently monitor and process large volumes of scientific literature on the subject. Currently, as the pandemic is winding down, the clinicians encountered a novel syndrome - Post-acute Sequelae of COVID-19 (PASC) - that affects over 10% of those who contract SARS-CoV-2 and presents a significant and growing challenge in the medical field. The continuous influx of new research publications underscores a critical need for efficient tools for navigating the literature. Objectives: We aimed to develop an application which will allow monitoring and categorizing COVID-19-related literature through building publication networks and medical subject headings (MeSH) maps to be able to quickly identify key publications and publication networks. Methods: We introduce CORACLE (COVID-19 liteRAture CompiLEr), an innovative web application designed for the analysis of COVID-19-related scientific articles and the identification of research trends. CORACLE features three primary interfaces: The "Search" interface, which displays research trends and citation links; the "Citation Map" interface, allowing users to create tailored citation networks from PubMed Identifiers (PMIDs) to uncover common references among selected articles; and the "MeSH" interface, highlighting current MeSH trends and associations between MeSH terms. Results: Our web application, CORACLE, leverages regularly updated PubMed data to aggregate and categorize the extensive literature on COVID-19 and PASC, aiding in the identification of relevant research publication hubs. Using lung function in PASC patients as a search example, we demonstrate how to identify and visualize the interactions between the relevant publications. Conclusion: CORACLE proves to be an effective tool for the extraction and analysis of literature. Its functionalities, including the MeSH trends and customizable citation mapping, facilitate the discovery of relevant information and emerging trends in COVID-19 and PASC research.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.03.18.584627v1" target="_blank">CORACLE (COVID-19 liteRAture CompiLEr): A platform for efficient tracking and extraction of SARS-CoV-2 and COVID-19 literature, with examples from post-COVID with respiratory involvement</a>
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</div></li>
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<li><strong>Young Parents’ Experiences of Pregnancy and Parenting during the COVID-19 Pandemic: A qualitative study in the United Kingdom</strong> -
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<div>
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Young parents (aged 16-24 years) in the perinatal period may be at an increased risk of poor mental health during the COVID-19 pandemic, due to multiple risk factors, including social and economic instability. COVID-19 related restrictions had significant implications for the delivery of some perinatal care services and other support structures for young parents. Investigating young parents’ experiences during the COVID-19 pandemic, including their perceived challenges and needs, is important to inform good practice and provide appropriate support for young parents. Qualitative interviews were conducted with young parents (n=21) during the COVID-19 pandemic in the United Kingdom from February – May 2021. Data were analysed using thematic analysis. Three key themes were identified to describe parents’ experiences during the COVID-19 pandemic. Parents reported specific COVID-19 related anxieties and stressors, including worries around contracting the virus and increased feelings of distress due to uncertainty created by the implications of the pandemic. Parents described feeling alone both at home and during antenatal appointments and highlighted the absence of social support as a major area of concern. Also, parents felt their perinatal care had been disrupted by the pandemic and experienced difficulties accessing care online or over the phone. This study highlights the potential impact of COVID-19 on young parents, including on their mental wellbeing and the perinatal support they were able to access during the pandemic. Insights from this study could inform the support and services offered to families during future pandemics. Specifically, the findings underlie the importance of (a) supporting both parents during perinatal appointments, (b) providing parents with early mental health support and (c) finding ways to facilitate communication pathways between professionals and parents.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/preprints/psyarxiv/h3b6y/" target="_blank">Young Parents’ Experiences of Pregnancy and Parenting during the COVID-19 Pandemic: A qualitative study in the United Kingdom</a>
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<li><strong>Demographic and health factors associated with pandemic anxiety in the context of COVID-19</strong> -
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Objectives The mental health consequences of COVID-19 are predicted to have a disproportionate impact on certain groups. We aimed to develop a brief measure, the Pandemic Anxiety Scale, to capture the specific aspects of the pandemic that are provoking anxiety, and explore how these vary by health and demographic factors. Design Data were from a convenience sample of parents (N=4,793) and adolescents (N=698) recruited in the first 6 weeks of lockdown. Methods Factor analytic and IRT methods were used to validate the new measure in both parent and adolescent samples. Associations between scores on the new measure and age, gender, household income, and physical health status were explored using structural equation modelling (SEM). Results Two factors were identified in both samples: disease-anxiety (e.g. catching, transmitting the virus) and consequence anxiety (e.g. impact on economic prospects), and unique associations with health and demographic factors were observed. Conclusions Anxieties due to the COVID-19 are multifaceted, and the PAS is a short, reliable and valid measure of these concerns. These anxieties are differentially associated with demographic, social and health factors, which should be considered when developing strategies to mitigate the mental health impact of the pandemic.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/preprints/psyarxiv/2eksd/" target="_blank">Demographic and health factors associated with pandemic anxiety in the context of COVID-19</a>
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<li><strong>A three-wave network analysis of COVID-19’s impact on schizotypal traits, paranoia and mental health through loneliness</strong> -
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<div>
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This manuscript is now published in open access UCL Open Environment: https://ucl.scienceopen.com/hosted-document?doi=10.14324/111.444/000092.v2 <strong>This manuscript has been submitted for publication and is likely to be edited as part of the peer-review process. Correspondence regarding this paper should be addressed to Keri Ka-Yee Wong, keri.wong@ucl.ac.uk.</strong> Background. The 2019 coronavirus (COVID-19) pandemic has impacted people’s mental wellbeing. Studies to date have examined the prevalence of mental health symptoms (anxiety, depression, loneliness), yet fewer longitudinal studies have compared across background factors and other psychological variables to identify vulnerable sub-groups. This study tests to what extent higher levels of psychotic-like experiences – indexed by schizotypal traits and paranoia – are associated with various mental health variables 6- and 12-months since April 2020. Methods. Over 2,300 adult volunteers (18-89 years, female=74.9%) with access to the study link online were recruited from the UK, USA, Greece, and Italy. Self-reported levels of schizotypy, paranoia, anxiety, depression, aggression, loneliness, and stress from three timepoints (17 April to 13 July 2020, N1 =1,599; 17 October to 31 January 2021, N2 =774; and 17 April to 31 July 2021, N3 =586) were mapped using network analysis and compared across time and background variables (sex, age, income, country). Results. Schizotypal traits and paranoia were positively associated with poorer mental health through loneliness, with no effect of age, sex, income levels, countries, and timepoints. Loneliness was the most influential variable across all networks, despite overall reductions in levels of loneliness, schizotypy, paranoia, and aggression during the easing of lockdown. Individuals with higher levels of schizotypal traits/paranoia reported poorer mental health outcomes than individuals in the low-trait groups. Conclusion. Schizotypal traits and paranoia are associated with poor mental health outcomes through self-perceived loneliness, suggesting that increasing social/community cohesion may improve individuals’ mental wellbeing in the long run.
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🖺 Full Text HTML: <a href="https://osf.io/preprints/psyarxiv/p9wrv/" target="_blank">A three-wave network analysis of COVID-19’s impact on schizotypal traits, paranoia and mental health through loneliness</a>
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<li><strong>The impact of the Covid-19 pandemic on young people from black and mixed-ethnic groups’ mental health: A qualitative study</strong> -
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Author Notes This is now published in BMJ Open on 5 May 2023: https://bmjopen.bmj.com/content/13/5/e071903.full <strong>This manuscript has been submitted for publication and is likely to be edited as part of the peer-review process. Correspondence regarding this paper should be addressed to Dr Keri Ka-Yee Wong, keri.wong@ucl.ac.uk</strong> Abstract Objectives The Covid-19 pandemic has disproportionately impacted vulnerable groups’ physical and mental health, especially young people and minority ethnic groups, yet little is known about how this is taking place and what support they would like. To address this gap, this qualitative study aims to uncover the effect of the Covid-19 outbreak on young people with ethnic minority backgrounds’ mental health, how this changed since the end of lockdown and what support they need to cope with these issues. Setting and Participants Ten 20-minute in-person semi-structured interviews were conducted with young people aged 12 to 17 years old from black and mixed-ethnic groups who regularly attend a community centre in West London. Results Through Interpretative Phenomenological Analysis, results indicated that the participants’ mental health was negatively impacted by the Covid-19 pandemic, with feelings of loneliness being the most common experience. However, positive effects were concurrently observed including improved well-being and better coping strategies post-lockdown, which is a testament to the young people’s resilience. That said, it is clear that young people from minority ethnic backgrounds lacked support during the Covid-19 pandemic and would now need psychological, practical and relational assistance to cope with these challenges. Conclusions Whilst future studies would benefit from a larger ethnically-diverse sample, this is a start. Study findings have the potential to inform future government policies around mental health support and access for young people from ethnic minorities, notably prioritising support for grassroots initiatives during times of crisis. Strengths and limitations • This qualitative interview study during Covid-19 gives voice to the experiences of young people from black and mixed-ethnic backgrounds in the UK • The in-person quality of the interviews helped build rapport between the researcher and the young people and sharing of sensitive issues around mental health access and support, increasing the results’ validity • This is a convenient sample, with girls and those aged 15 years and above being disproportionately represented in our data as they provided most of the answers. • The small sample size and lack of ethnic diversity limits the generalisability of the study to individuals from other ethnic minority groups.
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🖺 Full Text HTML: <a href="https://osf.io/fe36p/" target="_blank">The impact of the Covid-19 pandemic on young people from black and mixed-ethnic groups’ mental health: A qualitative study</a>
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<li><strong>Reflections, Resilience, and Recovery: A qualitative study of the COVID-19 impact on an international general population’s mental health and priorities for support</strong> -
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<strong>This paper is now published in open access UCL Open Environment: https://ucl.scienceopen.com/hosted-document?doi=10.14324/111.444/000119.v2</strong>* The impact of the coronavirus 2019 (COVID-19) pandemic on different countries and populations is well documented in quantitative studies, with some studies showing stable mental health symptoms and others showing fluctuating symptoms. However, the reasons behind why some symptoms are stable and others change are under-explored, which in turn makes identifying the types of support needed by participants themselves challenging. To address these gaps, this study thematically analysed 925 qualitative responses from five open-ended responses collected in the UCL-Penn Global COVID Study between 17 April to 31 July 2021 (wave 3). Three key themes comprised of 13 codes were reported by participants across countries and ages regarding the impact of COVID-19 on their health, both mental and physical, and livelihoods. These include: 1) Outlook on self/life, 2) Self-improvement, and 3) Loved ones (friends and family). In terms of support, while 2.91% did not require additional support, 91% wanted support beyond financial. Other unexpected new themes were also discussed regarding vulnerable populations suffering disproportionately. The pandemic has brought into sharp focus various changes in people’s mental health, physical health, and relationships. Greater policy considerations should be given to supporting citizens’ continued access to mental health when considering pandemic recovery. Keywords: COVID-19; mental health; behavioural change; qualitative; financial burden; support.
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🖺 Full Text HTML: <a href="https://osf.io/preprints/psyarxiv/8sdg4/" target="_blank">Reflections, Resilience, and Recovery: A qualitative study of the COVID-19 impact on an international general population’s mental health and priorities for support</a>
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<li><strong>Child Externalizing and Internalizing Behavior and Parental Well-Being During the COVID-19 Pandemic</strong> -
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Author Notes <strong>This manuscript is now published in open access UCL Open Environment: https://ucl.scienceopen.com/hosted-document?doi=10.14324/111.444/ucloe.000040</strong>. <strong>This manuscript has been submitted for publication and is likely to be edited as part of the peer-review process. Correspondence regarding this paper should be addressed to Keri Ka-Yee Wong, keri.wong@ucl.ac.uk.</strong> Abstract In this study we surveyed families’ experiences with parental depression, stress, relationship conflict, and child behavioral issues during six months of the COVID-19 pandemic through the COVID-19: Global Social Trust and Mental Health Study. The current analyses used data collected from online surveys completed by adults in 66 countries from April 17, 2020-July 14, 2020 (Wave I), followed by surveys six months later at Wave II (October 17, 2020-January 31, 2021). Analyses were limited to 175 adult parents who reported living with at least one child under 18 years old at Wave I. Parents reported on children’s level of externalizing and internalizing behavior at Wave I. At Wave II, parents completed self-reported measures of stress, depression, and inter-partner conflict. Child externalizing behavior at Wave I significantly predicted higher levels of parental stress and marginally predicted parental depression at Wave II, controlling for covariates. Child internalizing behavior at Wave I did not predict parental stress or depression, controlling for covariates. Neither child externalizing nor internalizing behavior predicted parental relationship conflict. The overall findings demonstrate that child behavior likely influenced parental stress and depression during the COVID-19 pandemic. Findings suggest that mental health interventions for children and parents may improve the family system during times of disaster.
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🖺 Full Text HTML: <a href="https://osf.io/preprints/psyarxiv/4tpsr/" target="_blank">Child Externalizing and Internalizing Behavior and Parental Well-Being During the COVID-19 Pandemic</a>
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<li><strong>Cell culture differentiation and proliferation conditions influence the in vitro regeneration of the human airway epithelium</strong> -
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The human airway mucociliary epithelium can be recapitulated in vitro using primary cells cultured in an Air-Liquid Interface (ALI), a reliable surrogate to perform pathophysiological studies. As tremendous variations exist between media used for ALI-cultured human airway epithelial cells, our study aimed to evaluate the impact of several media (BEGM, PneumaCult, "Half½" and "Clancy") on cell type distribution using single-cell RNA sequencing and imaging. Our work revealed the impact of these media on cell composition, gene expression profile, cell signaling or epithelial morphology. We found higher proportions of multiciliated cells in PneumaCult-ALI and Half½, stronger EGF signaling from basal cells in BEGM-ALI, differential expression of the SARS-CoV-2 entry factor ACE2, and distinct secretome transcripts depending on media used. We also established that proliferation in PneumaCult-Ex Plus favored secretory cell fate, showing the key influence of proliferation media on late differentiation epithelial characteristics. Altogether, our data offer a comprehensive repertoire for evaluating the effects of culture conditions on airway epithelial differentiation and will help to choose the most relevant medium according to the processes to be investigated such as cilia, mucus biology or viral infection. We detail useful parameters that should be explored to document airway epithelial cell fate and morphology.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.03.16.584842v1" target="_blank">Cell culture differentiation and proliferation conditions influence the in vitro regeneration of the human airway epithelium</a>
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<li><strong>Protein-based cell population discovery and annotation for CITE-seq data identifies cellular phenotypes associated with critical COVID-19 severity</strong> -
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Technologies such as Cellular Indexing of Transcriptomes and Epitopes sequencing (CITE-seq) and RNA Expression and Protein sequencing (REAP-seq) augment unimodal single-cell RNA sequencing (scRNA-seq) by simultaneously measuring expression of cell-surface proteins using antibody derived oligonucleotide tags (ADT). These protocols have been increasingly used to resolve cellular populations that are difficult to infer from gene expression alone, and to interrogate the relationship between gene and protein expression at a single-cell level. However, the ADT-based protein expression component of these assays remains widely underutilized as a primary tool to discover and annotate cell populations, in contrast to flow cytometry which has used surface protein expression in this fashion for decades. Therefore, we hypothesized that computational tools used for flow cytometry data analysis could be harnessed and scaled to analyze ADT data. Here we apply Ozette Discovery, a recently-developed method for flow cytometry analysis, to re-analyze a large (>400,000 cells) published COVID-19 CITE-seq dataset. Using the protein expression data alone, Ozette Discovery is able to identify granular, robust, and interpretable cellular phenotypes in a high-throughput manner. In particular, we identify a population of CLEC12A+CD11b+CD14- myeloid cells that are specifically expanded in patients with critical COVID-19, and can only be resolved by their protein expression profiles. Using the longitudinal gene expression data from this dataset, we find that early expression of interferon response genes precedes the expansion of this subset, and that early expression of PRF1 and GZMB within specific Ozette Discovery phenotypes provides a RNA biomarker of critical COVID-19. In summary, Ozette Discovery demonstrates that taking a protein-centric approach to cell phenotype annotation in CITE-seq data can achieve the potential that dual RNA/protein assays provide in mixed samples: instantaneous in silico flow sorting, and unbiased RNA-seq profiling.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.03.14.584720v1" target="_blank">Protein-based cell population discovery and annotation for CITE-seq data identifies cellular phenotypes associated with critical COVID-19 severity</a>
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<li><strong>Differential Patterns of Cross-Protection against Antigenically Distinct Variants in Small Animal Models of SARS-CoV-2 Infection</strong> -
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Continuous evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) will likely force more future updates of vaccine composition. Based on a series of studies carried out in human ACE2 transgenic mice (K18-hACE2) and Syrian hamsters, we show that immunity at the respiratory tract, acquired through either previous infection or vaccination with an in-house live attenuate virus, offers protection against antigenically distinct variants in the absence of variant spike-specific neutralizing antibodies. Interestingly, immunity acquired through infection of a modern variant (XBB.1.5) was insufficient in preventing brain infection by the ancestral virus (WA1/2020) in K18-hACE2 mice. Similarly, previous infection with WA1/2020 did not protect against brain infection by XBB.1.5. Our results highlight the importance of immune components other than neutralizing antibodies in maintaining protection against new variants in the respiratory tract, but also paint scenarios where a monovalent vaccine based on a contemporary variant may be less effective against the ancestral strain.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.03.14.584985v1" target="_blank">Differential Patterns of Cross-Protection against Antigenically Distinct Variants in Small Animal Models of SARS-CoV-2 Infection</a>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Valacyclovir Plus Celecoxib for Post-Acute Sequelae of SARS-CoV-2</strong> - <b>Conditions</b>: PASC Post Acute Sequelae of COVID 19; Long COVID <br/><b>Interventions</b>: Drug: 1500 Valacyclovir 200 Celecoxib; Drug: 750 Valacyclovir 200 Celecoxib; Drug: Placebo <br/><b>Sponsors</b>: Bateman Horne Center <br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Supervised Computerized Active Program for People With Post-COVID Syndrome (SuperCAP Study)</strong> - <b>Conditions</b>: Post-COVID Condition <br/><b>Interventions</b>: Device: SuperCAP Program <br/><b>Sponsors</b>: Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia; Institut de Recerca de la SIDA IrsiCaixa; Germans Trias i Pujol Hospital <br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Utilizing Novel Blood RNA Biomarkers as a Diagnostic Tool in the Identification of Long COVID-19</strong> - <b>Conditions</b>: Long COVID <br/><b>Interventions</b>: Diagnostic Test: RNA Biomarker Blood Test <br/><b>Sponsors</b>: MaxWell Clinic, PLC <br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Home-Based Circuit Training in Overweight/Obese Older Adult Patients With Knee Osteoarthritis and Type 2 Diabetes</strong> - <b>Conditions</b>: Aerobic Exercise; Strength Training; Glycemic Control; Blood Pressure; Oxidative Stress; Metabolic Syndrome <br/><b>Interventions</b>: Behavioral: 12-week home-based circuit training (HBCT); Behavioral: Standard of care (CONT) <br/><b>Sponsors</b>: Princess Nourah Bint Abdulrahman University <br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>RECOVER-AUTONOMIC Platform Protocol</strong> - <b>Conditions</b>: Long COVID; Long Covid19; Long Covid-19 <br/><b>Interventions</b>: Drug: IVIG + Coordinated Care; Drug: IVIG Placebo + Coordinated Care; Drug: Ivabradine + Coordinated Care; Drug: Ivabradine Placebo + Coordinated Care; Drug: IVIG + Usual Care; Drug: IVIG Placebo + Usual Care; Drug: Ivabradine + Usual Care; Drug: Ivabradine Placebo + Usual Care <br/><b>Sponsors</b>: Kanecia Obie Zimmerman <br/><b>Enrolling by invitation</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SVF for Treating Pulmonary Fibrosis Post COVID-19</strong> - <b>Conditions</b>: Pulmonary Fibrosis <br/><b>Interventions</b>: Biological: Autologous adipose-derived SVF IV administration <br/><b>Sponsors</b>: Michael H Carstens; Ministerio de Salud de Nicaragua; Wake Forest University; National Autonomous University of Nicaragua <br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>RECOVER-AUTONOMIC: Platform Protocol, Appendix B (Ivabradine)</strong> - <b>Conditions</b>: Long COVID; Long Covid19; Long Covid-19 <br/><b>Interventions</b>: Drug: Ivabradine; Drug: Ivabradine Placebo; Behavioral: Coordinated Care; Behavioral: Usual Care <br/><b>Sponsors</b>: Kanecia Obie Zimmerman <br/><b>Enrolling by invitation</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>RECOVER-AUTONOMIC: Platform Protocol, Appendix A (IVIG)</strong> - <b>Conditions</b>: Long COVID; Long Coronavirus Disease 2019 (Covid19); Long Covid-19 <br/><b>Interventions</b>: Drug: IVIG (intravenous immunoglobulin); Drug: IVIG Placebo; Behavioral: Coordinated Care; Behavioral: Usual Care <br/><b>Sponsors</b>: Kanecia Obie Zimmerman <br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Understanding Adaptive Immune Response After COVID-19 Vaccination Boosters to Improve Vaccination Strategies in Vulnerable Groups.</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Other: Analisys of cellular response and humoral response to SARS-CoV-2 vaccine booster doses <br/><b>Sponsors</b>: IRCCS Sacro Cuore Don Calabria di Negrar <br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>COVIDVaxStories: Randomized Trial to Reduce COVID-19 Vaccine Hesitancy in Populations of Color</strong> - <b>Conditions</b>: Vaccine Hesitancy <br/><b>Interventions</b>: Behavioral: Storytelling; Behavioral: Learn More (Active Comparator) <br/><b>Sponsors</b>: University of Massachusetts, Worcester; Merck Sharp & Dohme LLC <br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>An E-health Psychoeducation for People With Bipolar Disorders</strong> - <b>Conditions</b>: Bipolar Disorder; Psychoeducation; COVID-19 Pandemic <br/><b>Interventions</b>: Other: e-health psychoeducation <br/><b>Sponsors</b>: University of Cagliari; Alessandra Perra <br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Sulfureous Water Therapy in Viral Respiratory Diseases</strong> - <b>Conditions</b>: Long-COVID; Post COVID-19 Condition; Chronic COVID-19 Syndrome; Post Acute Sequelae of COVID-19 <br/><b>Interventions</b>: Other: Inhalation of Sulfurous Thermal Water; Other: Inhalation of Sterile Distilled non-pyrogenic Water <br/><b>Sponsors</b>: University of Roma La Sapienza; Università degli studi di Roma Foro Italico; Queen Mary University of London; Bios Prevention Srl <br/><b>Completed</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<ul>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Health-promoting benefits of lentils: Anti-inflammatory and anti-microbial effects</strong> - This paper describes how lentils (Lens culinaris species) can positively affect health by reducing inflammation, providing antioxidants, and displaying antimicrobial properties. Lentils are rich in proteins, essential amino acids, minerals, and fibers, making them a valuable source of nutrition, particularly in low and middle-income countries. Lentils have many health benefits, including positive effects on diabetes management, support for cardiovascular health, and antioxidative properties. The…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Happy Hour: The association between trait hedonic capacity and motivation to drink alcohol</strong> - The (over)consumption of alcohol and other addictive substances is often conceptualized as a problem of low self-control (i.e., people’s inability to inhibit unwanted impulses). According to that view, people drink because they cannot resist. In the present studies, we approached this from a different perspective and tested whether alcohol consumption might also be a problem of low hedonic capacity (i.e., people’s inability to experience pleasure and relaxation, often due to intrusive thoughts)….</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Compound C inhibits the replication of feline coronavirus</strong> - Feline Coronavirus (FCoV) is a viral pathogen of cats and a highly contagious virus. Cats in a cattery can be infected by up to 100%, and even household cats are infected by 20-60%. Some strains of FCoV are known to induce a fatal disease in cats named Feline Infectious Peritonitis (FIP). However, no effective treatments are available. We demonstrated that compound C (dorsomorphin) can potentially inhibit feline coronavirus replication. Compound C treatment decreased the FCoV-induced plaque…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Hyperoside inhibits EHV-8 infection via alleviating oxidative stress and IFN production through activating JNK/Keap1/Nrf2/HO-1 signaling pathways</strong> - Equine herpesvirus type 8 (EHV-8) causes abortion and respiratory disease in horses and donkeys, leading to serious economic losses in the global equine industry. Currently, there is no effective vaccine or drug against EHV-8 infection, underscoring the need for a novel antiviral drug to prevent EHV-8-induced latent infection and decrease the pathogenicity of this virus. The present study demonstrated that hyperoside can exert antiviral effects against EHV-8 infection in RK-13 (rabbit kidney…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Effect of polyphenols against complications of COVID-19: current evidence and potential efficacy</strong> - The COVID-19 pandemic that started in 2019 and resulted in significant morbidity and mortality continues to be a significant global health challenge, characterized by inflammation, oxidative stress, and immune system dysfunction.. Developing therapies for preventing or treating COVID-19 remains an important goal for pharmacology and drug development research. Polyphenols are effective against various viral infections and can be extracted and isolated from plants without losing their therapeutic…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Poly Aptamer Encoded DNA Nanocatcher Informs Efficient Virus Trapping</strong> - Broad-spectrum antiviral platforms are always desired but still lack the ability to cope with the threats to global public health. Herein, we develop a poly aptamer encoded DNA nanocatcher platform that can trap entire virus particles to inhibit infection with a broad antiviral spectrum. Ultralong single-stranded DNA (ssDNA) containing repeated aptamers was synthesized as the scaffold of a nanocatcher via a biocatalytic process, wherein mineralization of magnesium pyrophosphate on the ssDNA…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Unveiling the Antiviral Capabilities of Targeting Human Dihydroorotate Dehydrogenase against SARS-CoV-2</strong> - The urgent need for effective treatments against emerging viral diseases, driven by drug-resistant strains and new viral variants, remains critical. We focus on inhibiting the human dihydroorotate dehydrogenase (HsDHODH), one of the main enzymes responsible for pyrimidine nucleotide synthesis. This strategy could impede viral replication without provoking resistance. We evaluated naphthoquinone fragments, discovering potent HsDHODH inhibition with IC(50) ranging from 48 to 684 nM, and promising…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Targeting G9a translational mechanism of SARS-CoV-2 pathogenesis for multifaceted therapeutics of COVID-19 and its sequalae</strong> - By largely unknown mechanism(s), SARS-CoV-2 hijacks the host translation apparatus to promote COVID-19 pathogenesis. We report that the histone methyltransferase G9a noncanonically regulates viral hijacking of the translation machinery to bring about COVID-19 symptoms of hyperinflammation, lymphopenia, and blood coagulation. Chemoproteomic analysis of COVID-19 patient peripheral mononuclear blood cells (PBMC) identified enhanced interactions between SARS-CoV-2-upregulated G9a and distinct…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Soluble ACE2 correlates with severe COVID-19 and can impair antibody responses</strong> - Identifying immune modulators that impact neutralizing antibody responses against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is of great relevance. We postulated that high serum concentrations of soluble angiotensin-converting enzyme 2 (sACE2) might mask the spike and interfere with antibody maturation toward the SARS-CoV-2-receptor-binding motif (RBM). We tested 717 longitudinal samples from 295 COVID-19 patients and showed a 2- to 10-fold increase of enzymatically active…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Evaluating Critical Thinking Disposition, Emotional Intelligence, and Learning Environment of Nursing Students: A Longitudinal Study</strong> - CONCLUSIONS: Critical thinking and emotional intelligence did not change, but students favored the online learning environment over the traditional. These findings suggest that nurse educators persevered, adapted, and maintained the quality of the learning environment despite the pandemic. Moreover, the utilization of an online learning environment may have led to enhanced enjoyment and engagement for students, which could potentially result in improved learning outcomes.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Asiatic acid cyclodextrin inclusion micro-cocrystal for insoluble drug delivery and acute lung injury therapy enhancement</strong> - CONCLUSION: The micro-sized inclusion cocrystals AA/γCD were successfully delivered into the lungs by pulmonary administration and had a significant therapeutic effect on ALI.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Thai traditional medicines reduce CD147 levels in lung cells: Potential therapeutic candidates for cancers, inflammations, and COVID-19</strong> - CONCLUSIONS: UMD and UMM are potential for reduction of CD147 levels which provide a useful information for further development of UM as potential therapeutic candidates for CD147-associated diseases such as cancers, inflammations, and COVID-19.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Design, synthesis, and antiviral activity of 1-aryl-4-arylmethylpiperazine derivatives as Zika virus inhibitors with broad antiviral spectrum</strong> - Zika virus (ZIKV) disease has been given attention due to the risk of congenital microcephaly and neurodevelopmental disorders after ZIKV infection in pregnancy, but no vaccine or antiviral drug is available. Based on a previously reported ZIKV inhibitor ZK22, a series of novel 1-aryl-4-arylmethylpiperazine derivatives was designed, synthesized, and investigated for antiviral activity by quantify cellular ZIKV RNA amount using RT-qPCR method in ZIKV-infected human venous endothelial cells…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A combination of nirmatrelvir and ombitasvir boosts inhibition of SARS-CoV-2 replication</strong> - Antiviral therapeutics are highly effective countermeasures for the treatment of coronavirus disease 2019 (COVID-19). However, development of resistance to antivirals undermines their effectiveness. Combining multiple antivirals during patient treatment has the potential to overcome the evolutionary selective pressure towards antiviral resistance, as well as provide a more robust and efficacious treatment option. The current evidence for effective antiviral combinations to inhibit severe acute…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Novel nitric oxide donors are coronary vasodilators that also bind to the papain-like protease of SARS-CoV-2</strong> - Several investigational nitric oxide donors were originally created to correct vascular endothelial dysfunction in cardiovascular diseases. These 48 compounds contain an urea-like moiety attached to the well-known NO donors isosorbide 2- and 5-mononitrate. CR-0305 and CR-0202 were synthesized and found to be nontoxic in the cell lines HMEC-1, A549/hACE2 and VeroE6. CR-0305 induced vasodilation in human coronary arteries ex vivo. Since NO can also have antiviral properties, a study of…</p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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